Yokoyama H, Lingle D M, Crestanello J A, Kamelgard J, Kott B R, Momeni R, Millili J, Mortensen S A, Whitman G J
Department of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia, USA.
Surgery. 1996 Aug;120(2):189-96. doi: 10.1016/s0039-6060(96)80287-x.
Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism.
Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated.
I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion.
Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.
心脏缺血再灌注（I/R）损伤会导致冠状动脉血管功能障碍。辅酶Q10（CoQ）在I/R后可维持心脏机械功能，最近被认为是一种自由基清除剂。我们假设CoQ通过抗氧化机制保护I/R后的冠状动脉血管反应性。
实验前，大鼠分别用CoQ（20mg/kg肌肉注射和10mg/kg腹腔注射[CoQ组]）或赋形剂（对照组）进行预处理。将离体灌注的大鼠心脏进行25分钟的整体常温缺血和40分钟的再灌注。通过光泽精增强化学发光直接评估再灌注诱导的氧化爆发。在平衡时以及再灌注后，分别用内皮依赖性血管舒张剂缓激肽和非内皮依赖性血管舒张剂硝普钠（SNP）测量冠状动脉血流。还评估了冠状动脉内注入过氧化氢（H2O2，0.1μmol/g体重，持续5分钟）模拟I/R后的自由基爆发的效果，
I/R降低了缓激肽诱导的冠状动脉血流变化（平衡时为-5%±4%，而再灌注后为26%±3%；p<0.05）以及SNP诱导的血流变化（平衡时为+20%±6%，而再灌注后为+56%±5%；p<0.05）。注入H2O2后的冠状动脉血管舒张反应性也有类似的降低（对缓激肽的反应为+4%±4%，对SNP的反应为+35%±8%；与平衡时相比，p<0.05）。CoQ预处理可改善I/R后缓激肽诱导的血管舒张（+12%±2%；与对照I/R相比，p<0.05）或注入H2O2后的血管舒张（18%±4%；与对照I/R相比，p<0.05），但未能改善SNP诱导的血管舒张。CoQ预处理降低了再灌注早期I/R诱导的最大自由基爆发（9.3±0.8×10(3)cpm，而对照为11.5±1.1×10(3)cpm；p<0.05）。
内皮依赖性血管舒张比非内皮依赖性血管舒张对I/R损伤更敏感。通过直接抗氧化作用，CoQ通过提高对I/R损伤的耐受性来维持内皮依赖性血管舒张。
